Outline

Objective: Hormonally active pituitary adenomas are associated with severe systemic morbidities independent of local tumor effects. Even small remnants of residual hormone-producing tumors such as growth hormone-producing tumors will maintain the aberrant pathologic state. The purpose of the current study is to analyze whether tumor remnants can be identified using marker-free optical imaging technologies, namely Fourier-transformed infrared spectroscopy (FTIR). The first set of experiments aim to introduce a classification of different adenoma types and evaluate spectroscopic differences between HGH-active and inactive tumors, as well as to differentiate normal pituitary from adenoma tissue.

Methods: 21 HGH+ and 19 hormonally inactive pituitary adenomas as well as 4 normal pituitaries from autopsy tissue were snap frozen, sectioned on CaF2 glass slides and submitted to FTIR measurements using a dedicated system with a focal plane array detector. Parallel sections were submitted to H&E, HGH- and Ki67 immunohistochemistry.

Results: A classification algorithm based on a two-step supervised non-linear discriminant analysis was developed to distinguish different tumor components without labelling. The classification is based upon spectral features, which mainly arise within the spectral regions of 1000 bis 1260 cm-1, in particular containing phosphate and sugar components, within the amid-1 and -2 regions (1515 bis 1700 cm-1). Cross-validation was performed for all measurements.

Conclusions: A purely optical, completely label-free spectroscopic classification of normal pituitary tissue vs. adenoma is possible. Even within HGH+ adenomas, regions of differential hormone production are identified. This technology is currently advanced to allow in situ analyses of adenoma remnants via a fiber optic probe.